1. Field of the Invention
The present invention relates an automated peptide synthesizer, and more particularly to an automated peptide synthesizer having flow pathways for recovering unreacted acyl components and reaction solvents.
2. Discussion of the Related Art
Solid-phase peptide synthesis is a technique for synthesizing the desired peptide by repeating a step of deprotection and acyl component introduction in the process of sequential couplings of amino acids on a solid-phase support. This technique is basically one of chemical synthesis, in which a great excess of acyl components is sequentially reacted to permit the synthesis to proceed without confirmation of intermediates. The number of repeats of this synthesis step increases as the number of amino acids of the peptide chain increases, and because the remaining components such as acyl components remaining in the reaction product are potential contaminants for the following repeated synthesis step, they should be washed out with an organic solvent. This washing step requires an enormous amount of organic solvent For example, in the BOC method using methylene chloride, more than about 10 liters of the waste solvent is discharged when 1 g of a peptide consisting of 5 amino acid residues is synthesized.
Acyl components such as protected amino acids and protected peptide fragments are very expensive. Even when a 10-fold amount of the acyl components is used, 90% thereof is wasted since the amount of the acyl components actually involved in the reaction is theoretically equivalent. However, usually a 4-fold amount or more of the acyl components must be used in order to complete the reaction on a solid-phase support. This means that the cost of acyl components cannot be overlooked when a large-scale synthesis is employed, as contrasted with minor economic burden in experimentation or in a small-scale synthesis.
Also, solvents used for peptide synthesis such as dimethylformamide (DMF), methylene chloride, N-methylpyrrolidone and dimethylacetamide are not harmless substances and can cause environmental pollution when wasted, requiring an enormous amount of cost for their recovery and treatment. In particular, DMF, a frequently used solvent, is known to sometimes contain amine compounds as impurities and causes side reactions in the process of synthesis. Therefore, removal of trace amounts of amines and water from the reaction solvent allows synthesis at a high efficiency.